The overall goal of the proposed research is to develop new, efficient synthetic methodology, primarily involving transition metals, and to apply these new methods to the synthesis of biologically active compounds. The new methods will be developed to meet several important criteria, including simplicity, generality, flexibility, and high stereoselectivity. Each of these criteria is important, both to the ultimate applicability of the methodology to the synthesis of specific biologically active compounds, and to the overall utility of the new methodology to the evolution and study of new drugs, a process which involves systematic structure variations and extensive structure activity relationship studies. The specific aims are to develop synthetic methodology for the synthesis of antiviral 4'-substituted nucleoside analogs, antiviral carbocyclic nucleoside analogs, aminocyclitol and aminoglycoside antibiotics and glucosidase inhibitors, and to develop ways to chemically alter existing antiviral nucleosides to vary biological activity.